Cocaine addiction characterized by pathological motivation for drug abuse associated with a loss of control over cocaine seeking and use behaviors. Behavioral therapy approaches such as cognitive behavioral therapy (CBT) have proven to be efficacious in promoting recovery and relapse prevention, though their efficacy is limited. As a training vehicle, the proposed research plan would test a working hypothesis that enhanced glutamate neurotransmission facilitates the therapeutic learning and memory goals of addiction behavioral therapies and thus promotes recovery and relapse prevention. Aim 1 of the proposed research plan would use a placebo-controlled, randomized double-blind clinical trial design to determine if short-term, oral administration of the NMDA glutamate receptor partial agonist D-cycloserine (DCS) significantly enhances the relapse prevention, functional recovery, treatment retention and cocaine craving reduction goals of an extinction-based CBT. A hypothesis that DCS represents a useful adjunct to CBT in producing a significant and durable augmentation of relapse prevention would be tested. Aim 2 would determine whether there is a difference between treatment groups in the neural processing of attentional bias for drug cues or in the CBT-related engagement of brain areas involved in extinction learning and memory recall. A cocaine Stroop task (cocStroop) would be used to test a hypothesis that DCS potentiates the CBT-related extinction of the incentive properties of cocaine-predictive stimuli by enhancing the neural basis of extinction learning and memory retrieval. In aim 3 an exploratory pharmacogenetic imaging approach would explore the influence of allelic variation for common haplotypes of genes involved in endocannabinoid signaling that regulate extinction processes on the effect of DCS administration on treatment response and the neural response to conditioned drug cues. This aim would test a hypothesis that interindividual variability in treatment-related relapse prevention is attributed, in part, to sequence variation in endocannabinoid system genes. The long term goal of the proposed training plan is to establish a combination pharmacotherapy/psychotherapy approach to improve recovery and relapse prevention in cocaine and other addictions. The research conducted in the proposed training project will aid in the treatment of crack/cocaine addiction and could possibly shed light on addiction in general. The treatment of crack/cocaine addiction facilitated by psychotherapy with adjunct pharmacotherapy will also aid in decreasing recidivism in this drug-dependent population.